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Background and Aims: Women with primary ovarian insufficiency exhibit an unfavorable cardiovascular risk profile. A common cause for primary ovarian insufficiency is fragile X premutation (FXPC), and data on the cardiovascular risk factors in women with FXPC are scarce. We aimed to assess the prevalences of abnormal metabolic components among FXPC.Methods and Results: Clinical, anthropometric and laboratory data were collected from 71 women with FXPC and compared to 78 women referred for counseling in an in-vitro fertilization clinic (control group). The mean ± SD ages of the FXPC and control groups were 33.5 ± 5.6 and 36.2 ± 5.3 years, respectively (p = 0.003). In a logistic regression analysis, the FXPC group had increased risks for hyperglycemia, hypertriglyceridemia, central obesity and low high-density lipoprotein cholesterol, of 21.8-fold (95% CI 2.7-175, p = 0.004), 6.9-fold (95% CI 2.5-18.7, p < 0.0001), 3.1-fold (95% CI 1.4-6.9, p = 0.005) and 2.4-fold (95% CI 1.1-5.2, p = 0.03), compared to the control group. The FXPC group had 2.7-fold higher prevalence of two abnormal metabolic components; 19% met the full criteria of MetS, compared to 3% of the control group. Neither CGG repeats nor ovarian reserve markers were associated with metabolic risk.Conclusions: Carriers of fragile X premutation are at increased metabolic risk from early adulthood; waist circumference, glucose and lipid levels are particularly elevated. We recommend metabolic screening for all women with FMR1 premutation, to enable early interventions for prevention of long-term cardiovascular comorbidities. [ABSTRACT FROM AUTHOR]

Cancer risks in heterozygous mutation carriers of the ATM, BLM, and FANCC genes are controversial. To shed light on this issue, cancer rates were evaluated by cross referencing asymptomatic Israeli heterozygous mutation carriers in the ATM, BLM, and FANCC genes with cancer diagnoses registered at the Israeli National Cancer Registry (INCR). Comparison of observed to expected Standardized Incidence Rates (SIR) was performed. Overall, 474 individuals participated in the study: 378 females; 25 Arab and 31 Jewish ATM carriers, 152 BLM carriers, and 170 FANCC carriers (all Ashkenazim). Age range at genotyping was 19–53 years (mean + SD 30.6 + 5 years). In addition, 96 males were included; 5, 34, and 57 ATM, BLM, and FANCC mutation carriers, respectively. Over 5–16 years from genotyping (4721 person/years), 15 new cancers were diagnosed in mutation carriers: 5 breast, 4 cervical, 3 melanomas, and one each bone sarcoma, pancreatic, and colorectal cancer. No single cancer diagnosis was more prevalent then expected in all groups combined or per gene analyzed. Specifically breast cancer SIR was 0.02–0.77. We conclude that Israeli ATM, BLM, and FANCC heterozygous mutation carriers are not at an increased risk for developing cancer. [ABSTRACT FROM AUTHOR]

Objective: Arachnoid cysts (AC) are congenital lesions comprising 1% of all intracranial mass lesions. The aim of this study was to characterize arachnoid cysts and their neurodevelopmental outcome and to compare it with the outcome of children without AC.Methods: This is a retrospective cohort study of arachnoid cysts detected prenatally by fetal MRI in 29 fetuses compared to a control group of 59 fetuses without arachnoid cyst who were examined by MRI. The cohort was investigated from two different angles: anatomical and developmental. Anatomical analyzation, the cohort was divided into 2 groups by the arachnoid cyst anatomical location: group A (n = 9), which included cases with supratentorial cyst, and group B (n = 20), which included cases with infratentorial cyst. Developmental analyzation, the cohort was divided into 2 groups by the neurodevelopmental outcome: group γ (n = 5) which included cases that were affected by arachnoid cyst presence, and group δ (n = 17) which included cases that had neurodevelopmental outcome within the normal range. Data collected included prenatal history, MRI features, sonographic follow up, and neurodevelopmental outcome.Results: In 22/29 cases we achieved a long-term follow up, by evaluation of children development in a range of ages from 6 months to 6 years. In group A (n = 9), 4 infants had normal outcome, 2 had abnormal outcome, 1 pregnancy was terminated, and 2 cases were not cooperative with the study. In group B (n = 20), 13 infants had normal outcome, 3 had abnormal outcome, and 4 cases were not cooperative with the study.Conclusions: From all cases with AC detected by fetal MRI, 77.3% had normal neurodevelopmental outcome and 22.7% had abnormal neurodevelopment. [ABSTRACT FROM AUTHOR]

Abstract Diaphanospondylodysostosis (DSD) is a rare autosomal recessive skeletal disorder, characterized mainly by ossification defects in vertebrae, thorax malformations, renal cystic dysplasia and usually death in the perinatal period. DSD is caused by mutations in the bone morphogenetic protein-binding endothelial regulator (BMPER) gene. We describe the prenatal findings of a non-consanguineous Jewish couple (shared Balkan origin), with three affected fetuses that presented with malformations in the spine and chest, reduced ossification of the skull and spine, horseshoe kidney and increased nuchal translucency. The unique combination of these ultrasound (US) features raised the possibility of DSD, which was confirmed by whole exome sequencing (WES) performed on a single fetal DNA and familial segregation. In the three fetuses, a novel homozygous mutation in BMPER (c.410T > A; p.Val137Asp) was found. This mutation, which segregated in the family, was not found in 65 controls of Jewish Balkan origin, and in several large databases. Taken together, the combination of a detailed prenatal US examination and WES may be highly effective in confirming the diagnosis of a rare genetic disease, in this case DSD. [ABSTRACT FROM AUTHOR]